A transmission disequilibrium and linkage analysis of D22S278 marker alleles in 574 families: further support for a susceptibility locus for schizophrenia at 22q12. Schizophrenia Collaborative Linkage Group for Chromosome 22

Straub, R. E., Vallada, H., Curtis, D., Sham, P., Kunugi, H., Zhao, J. H., Murray, R., McGuffin, P., Nanko, S., Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Gill, M., Collier, D. A., Antonarakis, S., Housman, D., Kazazian, H., Nestadt, G., Pulver, A. E., MacLean, C. J., Walsh, D., Kendler, K. S., DeLisi, L., Polymeropoulos, M., Coon, H., Byerley, W., Lofthouse, R., Gershon, E., Goldin, L., Freedman, R., Laurent, C., Bodeau-Pean, S., d'Amato, T., Jay, M., Campion, D., Mallet, J., Wildenauer, D. B., Lerer, B., Albus, M., Ackenheil, M., Ebstein, R. P., Hallmayer, J., Maier, W., Gurling, H., Curtis, D., Kalsi, G., Brynjolfsson, J., Sigmundson, T., Petursson, H., Blackwood, D., Muri, W., StClair, D., He, L., Maguire, S., Moises, H. W., Hwu, H. G., Yang, L., Wiese, C., Kristbjarnarson, H., Levinson, D. F., Mowry, B. J., Donis-Keller, H., Hayward, N. K., Crowe, R. R., Silverman, J. M., Nancarrow, D. J. and Read, C. M. 1998. A transmission disequilibrium and linkage analysis of D22S278 marker alleles in 574 families: further support for a susceptibility locus for schizophrenia at 22q12. Schizophrenia Collaborative Linkage Group for Chromosome 22. Schizophrenia Research 32 (2) , pp. 115-121. 10.1016/S0920-9964(98)00048-6

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Abstract

Patients with schizophrenia rarely develop rheumatoid arthritis, an autoimmune disease that exhibits genetic association with the HLA DRB1*04 gene. We previously investigated the hypothesis that schizophrenia is negatively associated with DRB1*04, and found that only half the expected number of schizophrenic patients had this gene when compared with controls. We now report the results of DRB1*04 genotyping in pedigrees multiply affected with schizophrenia. Polymerase chain reaction amplification and sequence-specific oligonucleotide probes were used to determine the DRB1 genotypes of the 187 members of 23 pedigrees multiply affected with RDC schizophrenia. DQA1, DQB1 and DPB1 genotypes were similarly determined. We analysed data using the extended transmission/disequilibrium test and found a trend for the preferential non-transmission of DRB1*04 alleles from heterozygous parents to their schizophrenic offspring (16 of 23 alleles not transmitted, chi 2 = 3.5, p = 0.06). We found no evidence for a gene of major effect using GENEHUNTER for parametric and non-parametric linkage analysis. The results from this small sample need to be interpreted with caution, but they are in keeping with previous reports and suggest that HLA DRB1*04 alleles may be associated with a reduced risk of schizophrenia.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Elsevier
ISSN:	0920-9964
Last Modified:	31 Oct 2022 09:35
URI:	https://orca.cardiff.ac.uk/id/eprint/81634

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